小柯机器人

美国辉瑞公司Danna M. Breen小组近日取得一项新成果。他们发现在小鼠和非人类灵长类动物中和生长分化因子15（GDF-15）可减轻铂类化学药物引起的呕吐、厌食以及体重减轻。这一研究成果于2020年11月17日在线发表在《细胞-代谢》上。

研究人员探究了在小鼠和/或非人类灵长类动物模型中，GDF-15阻滞对铂类化学药引起的呕吐、厌食和体重减轻的影响。研究发现，在接受铂类化学疗法治疗的癌症患者中，循环系统中GDF-15的含量较高，并且与大肠癌患者的体重减轻呈正相关（NCT00609622）。

此外，与高催吐药评分相关的化学治疗剂可诱导小鼠循环GDF-15升高和体重减轻。在GDF-15敲除的小鼠中，铂类药物引起的厌食症和体重减轻得到缓解，并且单克隆抗体mAB1中和GDF-15可以提高存活率。在非人类灵长类动物中，mAB1治疗可减轻厌食和呕吐。这些结果表明，GDF-15阻滞是减轻化疗引起的副作用以及改善生活质量的潜在方法。

据悉，铂类癌症治疗药具有剂量依赖性副作用，这与GDF-15的升高有关。但是尚不清楚这种升高是否会导致这些副作用。

附：英文原文

Title: GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates

Author: Danna M. Breen, Hanna Kim, Donald Bennett, Roberto A. Calle, Susie Collins, Ryan M. Esquejo, Tao He, Stephanie Joaquim, Alison Joyce, Matthew Lambert, Laura Lin, Betty Pettersen, Shuxi Qiao, Michelle Rossulek, Gregory Weber, Zhidan Wu, Bei B. Zhang, Morris J. Birnbaum

Issue&Volume: 2020-11-17

Abstract: Platinum-based cancer therapy is restricted by dose-limiting side effects and is associatedwith elevation of growth differentiation factor 15 (GDF-15). But whether this elevationcontributes to such side effects has been unclear. Here, we explored the effects ofGDF-15 blockade on platinum-based chemotherapy-induced emesis, anorexia, and weightloss in mice and/or nonhuman primate models. We found that circulating GDF-15 is higherin subjects with cancer receiving platinum-based chemotherapy and is positively associatedwith weight loss in colorectal cancer (NCT00609622). Further, chemotherapy agentsassociated with high clinical emetic score induce circulating GDF-15 and weight lossin mice. Platinum-based treatment-induced anorexia and weight loss are attenuatedin GDF-15 knockout mice, while GDF-15 neutralization with the monoclonal antibodymAB1 improves survival. In nonhuman primates, mAB1 treatment attenuates anorexia andemesis. These results suggest that GDF-15 neutralization is a potential therapeuticapproach to alleviate chemotherapy-induced side effects and improve the quality oflife.

DOI: 10.1016/j.cmet.2020.10.023

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30592-1

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